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Biomedical subjects

K Larsen

Publications and source records attributed to K Larsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

A new class of plant homeobox genes is expressed in specific regions of determinate symbiotic root nodules.

A cDNA containing a homeobox sequence was isolated from a soybean nodule-specific expression library. This homeobox cDNA, Ndx (nodulin homeobox), represents a small gene family with at least two members in soybean (Glycine max) and three in Lotus japonicus. One complete 3304 bp Ndx cDNA from L. japonicus encodes a protein, NDX, of 958 amino acids. An unusual type of homeodomain that differs in two of the most conserved amino acid positions in the consensus sequence is located close to the C-terminal and appears to be the only DNA-binding domain. Weak Ndx gene expression in the root increases very shortly after infection with Rhizobium and remains throughout nodule development. In situ hybridizations show cell-specific expression patterns that suggest developmentally separate regions in maturing determinate nodules. Thus in the maturing nodule Ndx and leghemoglobin genes are expressed in a mutually exclusive fashion. The Ndx transcript is also detectable in the young nodule primordium. Ndx expression is not confined to the root nodule since Ndx is also expressed in shoot and root meristems, indicating that the Ndx gene products might also be involved in developmental processes in other plant tissues.

Amino Acid Sequence↗
PubMed1999

Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated from rat duodenum.

The effect of bradykinin on the cytosolic Ca2+ concentration were measured in single, Fura-2 loaded, smooth muscle cells isolated from rat duodenum. All cells responded with a Ca2+ signal when exposed to bradykinin. The bradykinin response consisted of an initial Ca2+ spike followed by a plateau. Pre-treatment of single muscle cells with either the phospholipase C blocker U-73122 or thapsigargin, which is a potent inhibitor of the endoplasmic reticulum Ca2+-ATPase, inhibited the response to bradykinin. Pre-treatment of the cells with EGTA or La3+ to inhibit the Ca2+ influx, abolished the response induced by bradykinin. We conclude that bradykinin applied to single smooth muscle cells from rat duodenum, increases cytosolic Ca2+ by emptying intracellular Ca2+ stores, and by contribution from extracellular Ca2+. In contrast to bradykinin-induced response in isolated rat duodenum (a relaxation followed by a contraction), we did not observe a biphasic effect of bradykinin on cytosolic Ca2+ in single muscle cells. Bradykinin may thus cause relaxation of duodenal smooth muscle indirectly through an effect on neighbouring cells as dilatation is brought about by this agent in blood vessels.

Animals↗
PubMed1999

Treatment and rehabilitation on a stroke unit improves 5-year survival. A community-based study.

BACKGROUND AND PURPOSE: We have previously reported a marked reduction in mortality up to 1 year after treatment and rehabilitation on a stroke unit versus on general neurological and medical wards in unselected stroke patients. In the present study we wanted to test the hypothesis that this mortality-reducing effect is not temporary but is long lasting. METHODS: We performed a community-based comparison of outcome in 1241 stroke patients from 2 adjacent communities in Copenhagen: in one (Frederiksberg), treatment and rehabilitation were provided on general neurological and medical wards, and in the other (Bispebjerg), treatment and rehabilitation were provided on a single large stroke unit. RESULTS: The 2 stroke populations were comparable regarding age, sex, initial stroke severity, lesion diameter on CT, and stroke subtype (hemorrhage/infarct), but patients treated on the stroke unit had a higher frequency of comorbidity and lower incomes. One-year mortality was 39% (general wards) versus 32% (stroke unit) (P=0.01). This difference was still present 5 years after stroke (71% versus 64%; P=0.02). In a multiple logistic regression model of 5-year mortality, treatment on a stroke unit reduced the relative risk of death by 40% (odds ratio, 0.60; 95% CI, 0.42 to 0.85; P<0.01), independent of age, sex, stroke severity, and comorbidity. CONCLUSIONS: The mortality-reducing effect of treatment and rehabilitation on a dedicated stroke unit is long lasting rather than temporary. Stroke unit treatment reduced the relative risk of death within 5 years after stroke by 40% in an unselected, community-based stroke population. These results emphasize the need for organization of treatment and rehabilitation of unselected stroke patients on dedicated stroke units.

Aged↗
PubMed1999

Epidemiology of juvenile chronic arthritis: risk dependent on sibship, parental income, and housing.

OBJECTIVE: We studied the socioeconomic background of children with juvenile chronic arthritis (JCA) diagnosed during the years 1988-91 in Denmark. The working hypothesis is that JCA may be triggered by one or several different infectious agents and that the amount of exposure to infectious agents in infancy and childhood affects the risk of JCA. METHODS: In this case-control study, we investigated socioeconomic variables prior to disease onset from national registers, primarily the Fertility Database of Statistics Denmark, in a national cohort of all 220 known cases of JCA fulfilling the EULAR criteria incident during the years 1988-91, identified from national and local diagnosis registers. There were 4 controls per case, matched for sex, age, and county of residence. Socioeconomic variables as risk factors were quantified by odds ratios, which are equivalent to relative risks of contracting JCA if exposed to a risk factor. RESULTS: Three socioeconomic variables were significantly and mutually independently associated with the risk of developing JCA during the following year. An only child had a risk of JCA 1.6 times that of a child with siblings. Children whose parents had a high income had a relative risk of 1.9. Children living in an urban flat had a risk 2.7 times that of children living on a farm. We found no space-time clustering of cases and no cyclical variations of incidence rates. CONCLUSION: The absence of clustering and of seasonal variation does not support a theory of triggering by infection. The hitherto unreported effects of the socioeconomic variables on the risk of JCA are of the same order of magnitude as reported for certain HLA alleles. Our findings do not lend full support to either of the 2 mechanisms, that growing up under either hygienic or unhygienic conditions increases the risk of JCA, and lack an obvious biological explanation.

Adolescent↗
PubMed1999

Effects of feeding on the circadian rhythm of Ceratophyllus s. sciurorum (Siphonaptera: Ceratophyllidae).

Circadian rhythm in newly emerged blood-fed individuals of the flea Ceratophyllus s. sciurorum was studied in a constant environment, using an insect activity monitor. The results of trials run continuously over seven days confirmed the finding that C. s. sciurorum has a self-sustaining clock. Statistical tests confirm that feeding weakens the rhythm but does not eliminate it. There was a significant difference in the mean activity between the fed and unfed fleas, reflecting the difference in the number of hours over which this activity took place. A possible commercial application for the monitor and also for the method of analysis is discussed.

Animals↗
PubMed1998

Intestinal parasites in swine in the Nordic countries: prevalence and geographical distribution.

In Denmark (DK), Finland (FIN), Iceland (I), Norway (N), and Sweden (S), 516 swine herds were randomly selected in 1986-1988. Individual faecal analyses (mean: 27.9 per herd) from eight age categories of swine showed that Ascaris suum, Oesophagostomum spp., Isospora suis, and Eimeria spp. were common, while Trichuris suis and Strongyloides ransomi-like eggs occurred sporadically. Large fatteners and gilts were most frequently infected with A. suum with maximum prevalences of 25-35% in DK, N and S, 13% in I and 5% in FIN. With the exception of the remarkably low A. suum prevalence rates in FIN, no clear national differences were observed. Oesophagostomum spp. were most prevalent in adult pigs in the southern regions (21-43% in DK and southern S), less common in the northern regions (4-17% adult pigs infected), and not recorded in I. I. suis was common in piglets in DK, I, and S (20-32%), while < 1% and 5% were infected in N and FIN, respectively. Eimeria spp. had the highest prevalences in adult pigs (max. 9%) without clear geographical differences. I. suis and Eimeria spp. were recorded for the first time in I, and I. suis for the first time in N.

Age Factors↗
PubMed1998

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

Abdomen↗
PubMed1998

The effect of catalase amplification on immortal lens epithelial cell lines.

Utilizing a human beta-actin promoter, a catalase cDNA expression vector was constructed. This construct was used to transfect two immortal cell lines, mouse alpha TN4-1 and rabbit N/N 1003A. The catalase activity was increased about 3.4 fold in the alpha TN4-1 cells and 38 fold in the N/N 1003A cells. Some changes in other enzyme activities were also observed as a result of the transfections. Surprisingly, the ability to degrade H2O2 in the extracellular environment of the cells did not markedly change as a result of the catalase amplification. However, the ability to resist H2O2 stress was dramatically altered. Non-protein thiol (NP-SH) levels, choline uptake and glyceraldehyde phosphate dehydrogenase (GPD) activity were all markedly decreased in the non-transfected cells when they were subjected to 300 microM H2O2. However, in both transfected cell lines, these parameters remained in the normal range during H2O2 stress. The results obtained upon observing aspects of DNA metabolism were more complicated. While on H2O2 stress, non-transfected cell lines showed a marked decrease in thymidine incorporation, only the transfected alpha TN4-1 line remained in the normal range. Thymidine incorporation in transfected rabbit N/N 1003A cells was decreased compared to normal cells. In contrast, studies on single strand DNA breaks indicated that transfected rabbit cells had little damage compared to the significant DNA damage observed in the normal cells. The normal N/N 1003A cells were also much more susceptible to H2O2 induced damage than normal alpha TN4-1 cells, suggesting that the high GSH peroxidase activity observed in the rabbit cells may be detrimental since the low glutathione reductase activity in such cells results in an accelerated depletion of glutathione. The overall results suggest that augmenting lens catalase may prevent cataract development caused by H2O2 stress.

Animals↗
PubMed1998

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

Aged↗
PubMed1998

IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils.

We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.

Calcium↗
PubMed1997

Glucocorticoid treatment for nasal polyps. The use of topical budesonide powder, intramuscular betamethasone, and surgical treatment.

BACKGROUND: The treatment of nasal polyps is controversial, and medical treatment alone has been little investigated to our knowledge. OBJECTIVE: To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone. DESIGN: Randomized, double-blind comparison of 2 dosages and additional treatment, if therapy failed. After 1 year, treatment with medication was stopped, and the demand for renewed treatment was monitored for another year. PATIENTS: Patients with bilateral nasal polyps who demanded treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice. During a 15-month period from 1990 to 1992, a total of 126 patients entered the 2-year study. INTERVENTIONS: In phase 1, randomized and double-blind treatment with a topical medication, budesonide powder, 800 micrograms or 400 micrograms daily, or a placebo was given for 1 month. In phase 2, randomized and double-blind treatment with budesonide powder, 800 micrograms or 400 micrograms daily, was given. At the end of phase 1, failed therapy was supplemented by randomly assigned treatment of either surgical removal or a single injection of sustained released betamethasone. In phase 3, treatment with the medication was discontinued, and patients were monitored for another year. The time when treatment was required again was noted. The present article deals with phases 2 and 3. MAIN OUTCOME MEASURES: Patients' scores of treatment efficacy as well as symptoms and signs. Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow. RESULTS: In all outcome measures, a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy. The clinical course was described at the end of phase 2. About 85% of the patients, including those who received additional therapy because the initial therapy failed, rated total or substantial control over the symptoms. The 2 dosages investigated showed equal results. These findings were consistent with the signs recorded and the peak expiratory flow rate index. The results of phase 3 showed that 50% of patients had demanded treatment after 4 months, while 34% managed without medication after 1 year. CONCLUSIONS: The clinical course in this study showed that most patients with nasal polyps do well with medical treatment. Therefore, surgery was required in few patients. However, the potential of medical treatment should be further explored in future studies.

Administration, Inhalation↗
PubMed1997

A long-term follow-up study of nasal polyp patients after simple polypectomies.

A long-term follow-up study was performed on randomly selected patients after simple snare polypectomies. There were 243 patients, of whom 211 underwent endoscopic examination. There were 154 males and 57 females and median age was 57.7 years. Median period of follow-up was 8 years (range, 38-145 months). The median number of polypectomies was 1.6 (range, 1-15). Polyp eosinophilia was recorded in 97% of the cases. From life-table analysis the 5-year rate for two or less polypectomies was 80% (95% confidence intervals, 75-86%). Symptoms and findings were recorded at a median time of 56 months from the last polypectomy. At this time 70% of the patients denied blocked nose or excessive secretions. Seventeen per cent of the group claimed loss of sense of smell, while 28% stated that it was poor. At follow-up, large polyps were found in 3% of the patients, moderately sized ones in 30% and small in 42%. No polyps were visible in 25%. Patients with asthma (26%) had more polypectomies than those without (median, 2.4 versus 1.4). Patients with a history of non-steroidal antiinflammatory drug intolerance (7%) had the highest number of polypectomies. Previous troublesome sinusitis and allergy seemed not to exert major influence on the number of polypectomies needed. In the primary care of nasal polyp patients, the majority only need minor or limited surgery or only medical treatment.

Adult↗
PubMed1997

Chlamydia pneumoniae in children with otitis media.

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.

Acute Disease↗
PubMed1997

Interleukin-8 and chemotactic activity of middle ear effusions.

The importance of interleukin (IL)-8 in the chemotactic activity of middle ear effusions (MEEs) was evaluated. There was a significantly higher IL-8 concentration in MEEs of children with acute otitis media (AOM) (n = 17; 136 ng/mL) than in children with otitis media with effusion (OME) (n = 28; 65 ng/mL). The IL-8 concentration in MEEs with bacteria (149 ng/mL) was significantly higher than in MEEs without bacteria (66 ng/mL). MEEs from children with AOM and OME had equally higher chemotactic activity than the diluent alone (23.3% and 24.8% vs. 9.2%). The chemotactic activity was not altered by the presence of bacteria nor did it correlate with IL-8 concentration. Fractionation of MEEs by gel chromatography demonstrated that the main chemotactic activity could clearly be separated from the IL-8 activity, thus excluding IL-8 as a main chemotactic component in MEEs.

Bacterial Infections↗
PubMed1997

Influenza virus M1 protein binds to RNA through its nuclear localization signal.

The RNA-binding activity of influenza A virus M1 protein was studied by cross-linking the protein to viral RNA followed by sequence analysis of the oligoribonucleotide bound to the protein as well as sequence analysis of the M1 peptide bound to the RNA. M1 was found to bind to RNA without any RNA sequence specificity, as verified in a series of filter-binding experiments using a large variety of nucleic acids including DNA. The peptide sequence that bound to the RNA was the RKLKR nuclear localization signal of M1. Site-specific mutagenesis of recombinant M1 showed that most of the basic residues in that region had to be mutated in order to inhibit RNA-binding. We also constructed an M1 mutant that no longer bound to RNA but which was still able to inhibit the in vitro transcription activity of isolated viral ribonucleoprotein, albeit to a lower extent. Mutation of the zinc-binding sequence had no effect on RNA-binding or transcription-inhibition activity.

Amino Acid Sequence↗
PubMed1997

Plasminogen activators in human nasal polyps and mucosa.

Fibrinolysis is one of the processes that are involved in inflammation. In this study we have investigated if it is also involved in bilateral nasal polyposis, a disease with an inflammatory component. Fibrinolytic activity in the nasal mucosa and nasal polyps has been studied in 10 patients with bilateral nasal polyposis. Tissue-type plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) activities and antigen levels have been determined in polyp tissue and control nasal mucosa. t-PA activity is higher in nasal mucosa (median: 4.26 i.u./mg) as compared with nasal polyps (median: 0.65 i.u./mg; p = 0.03); u-PA activity is slightly lower in nasal mucosa (median: 0.040 i.u./mg) as compared to polyps (median: 0.065 i.u./mg; not significant). The percentage of u-PA to t-PA is 7.9% in nasal mucosa and 22.8% in nasal polyps (p < 0.01). The shift towards a higher u-PA/t-PA ratio in nasal polyps suggests an inflammatory process. Plasma levels of C-reactive protein are all within normal limits, which may suggest that PA activity is restricted to a local inflammatory reaction in the airway mucosa. The higher u-PA/t-PA ratio in nasal polyps and the higher levels of u-PA, when compared with the findings in other organs affected by inflammation, indicate that u-PA plays a part in the inflammatory events resulting in nasal polyps.

Adult↗
PubMed1997

Regulations as Prevention Strategies for Shiftwork Problems.

The study examines how the Danish system of regulations stemming from collective agreements and legislation and its associated participatory structures operate at the local level in relation to shiftwork and health and safety issues in a regional hospital system consisting of seven hospitals. The study analyzed ward reports of each employee's employment and working hours, local agreements about working time for deviations from legislation, and accounts from meetings in Co-operation Committees and Health and Safety Committees with respect to shiftwork issues from 1980 to 1994. The results showed that part-time employment, especially for those working on fixed evening and night shifts, was a dominant feature in the shiftwork arrangements. A majority of wards were found to have mixtures of employees working rotating or fixed shifts. Each hospital had local agreements that extended the number of work days between periods with days off and reduced the daily resting period to its minimum. None of the meetings of the Health and Safety Committees dealt with shiftwork, and when shiftwork and working time were on the agendas of the Co-operation Committees, health and safety aspects did not feature in the conclusions. The absence of consideration of health and safety aspects is discussed in relation to the uncertainty of the general regulatory principles for work organization and scheduling. The paper concludes that in order to utilize the potential af the participatory structures in developing prevention strategies for shiftwork problems, it is important to clarify responsibilities and cooperation between the two participatory committees.

Journal Article↗